The overall objectives of this study are: (1) To define the biochemical and functional properties of mammalian cells in vitro that are most generally associated with cellular malignancy in vivo, as determined by cellular tumorigenicity in the athymic nude mouse. (2) To apply somatic cell genetic techniques to investigate the role of somatic mutation and chromosome segregation in malignant transformation of human diploid cell strains in vitro. (3) To identify and characterize the control mechanisms that are involved in tumor growth and metastasis in athymic nude mice carrying heterologous malignant tumors. Specifically, we will investigate the tumor cell-specific growth properties that are associated with invasive and metastatic spread, and the host-dependent immunological functions that control the metastatic behavior of potentially metastatic tumors.